Genetic Variant EFHC2:p.Asp742Glu (chrX-44148819-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025184.4(EFHC2):c.2226C>A(p.Asp742Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

EFHC2
NM_025184.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06

Publications

0 publications found

Variant links:

Genes affected

EFHC2 (HGNC:26233): (EF-hand domain containing 2) This gene encodes a protein which contains three DM10 domains and three calcium-binding EF-hand motifs. A related protein is encoded by a gene on chromosome 6. It has been suggested that both proteins are involved in the development of epilepsy (PMID: 15258581, 16112844) and that this gene may be associated with fear recognition in individuals with Turner syndrome. [provided by RefSeq, Aug 2011]

EFHC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08260822).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025184.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFHC2	NM_025184.4	MANE Select	c.2226C>A	p.Asp742Glu	missense	Exon 15 of 15	NP_079460.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EFHC2	ENST00000420999.2	TSL:1 MANE Select	c.2226C>A	p.Asp742Glu	missense	Exon 15 of 15	ENSP00000404232.2
EFHC2	ENST00000937700.1		c.2133C>A	p.Asp711Glu	missense	Exon 14 of 14	ENSP00000607759.1
EFHC2	ENST00000889038.1		c.2100C>A	p.Asp700Glu	missense	Exon 15 of 15	ENSP00000559097.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1070563

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

347381

African (AFR)

AF:

0.00

AC:

AN:

25797

American (AMR)

AF:

0.00

AC:

AN:

31257

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18819

East Asian (EAS)

AF:

0.00

AC:

AN:

28955

South Asian (SAS)

AF:

0.00

AC:

AN:

50070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38987

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4104

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

827456

Other (OTH)

AF:

0.00

AC:

AN:

45118

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0010

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.015

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.39

M_CAP

Benign

0.0041

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

-1.1

PrimateAI

Benign

0.48

REVEL

Benign

0.15

Sift4G

Benign

0.24

Polyphen

0.14

Vest4

0.31

MutPred

0.41

Gain of methylation at K741 (P = 0.0762)

MVP

0.24

MPC

0.14

ClinPred

0.13

GERP RS

-11

Varity_R

0.15

gMVP

0.47

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over